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Background: The Ministry of Health in Malawi is implementing a pragmatic and innovative approach for the management of all HIV-infected pregnant women, termed Option B+, which consists of providing life-long antiretroviral treatment, regardless of their CD4 count or clinical stage. Our objective was to determine if Option B+ represents a cost-effective option. Methods: A decision model simulates the disease progression of a cohort of HIV-infected pregnant women receiving prophylaxis and antiretroviral therapy, and estimates the number of paediatric infections averted and maternal life years gained over a ten-year time horizon. We assess the cost-effectiveness from the Ministry of Health perspective while taking into account the practical realities of implementing ART services in Malawi. Results: If implemented as recommended by the World Health Organization, options A, B and B+ are equivalent in preventing new infant infections, yielding cost effectiveness ratios between US$ 37 and US$ 69 per disability adjusted life year averted in children. However, when the three options are compared to the current practice, the provision of antiretroviral therapy to all mothers (Option B+) not only prevents infant infections, but also improves the ten-year survival in mothers more than four-fold. This translates into saving more than 250,000 maternal life years, as compared to mothers receiving only Option A or B, with savings of 153,000 and 172,000 life years respectively. Option B+ also yields favourable incremental cost effectiveness ratios (ICER) of US$ 455 per life year gained over the current practice. Conclusion: In Malawi, Option B+ represents a favorable policy option from a cost-effectiveness perspective to prevent future infant infections, save mothers’ lives and reduce orphanhood. Although Option B+ would require more financial resources initially, it would save societal resources in the long-term and represents a strategic option to simplify and integrate HIV services into maternal, newborn and child health programmes. © 2013 Fasawe et al.
A decision analytic model was developed to compare the costs, health outcomes and cost-effectiveness of WHO PMTCT Options A and B as well as Option B+ in Malawi for all HIV-infected pregnant women. The analysis was structured as a probability tree starting with an HIV-infected pregnant woman entering into contact with the health system for antenatal care, then receiving a cascade of interventions towards reducing the risk of transmission to her infant as well as care and treatment for her own health (Figure 1). The risk of transmission depends on the background HIV transmission rates during pregnancy, labour, delivery and breastfeeding, the efficacy of the antiretroviral drugs in preventing transmission, prophylaxis and treatment coverage and the level of adherence. The estimated number of HIV-infected pregnant women in Malawi was taken as the midpoint of the range reported for the end of 2010 [2] and this number, 66,500, was then used as an input to analyse as an annual cohort of HIV-infected pregnant women that, after surviving childbirth, was followed over a 10-year time horizon. This time horizon was thought to be sufficiently long enough to capture the effects of immediate or later access to treatment and to assess maternal survival outcomes. The patterns of disease progression in HIV-infected pregnant women with and without ART were assumed to be similar to that documented in the general adult population. A Markov model was developed to simulate the natural history of HIV infection and project the 10-year maternal outcomes associated with the different options implemented. The model assumes that women are treatment naïve and in one of four transition states: (a) CD4 counts >350 cells/ µL; (b) CD4 counts 350–200 cells/ µL; (c) CD4 between 199–0 cells/ µL and (d) death, as the absorbing state. Women starting with high CD4 counts and subsequently becoming eligible for ART when their CD4 cell counts fall to 350 or below, would access ART services when they move into the eligible transition state, while women eligible for treatment receive life-long therapy and are accounted for in the PMTCT programme. As more women access ART services in the future, the background survival rates of HIV-infected mothers under Options A and B improve when compared to the no-treatment scenario. Outcomes assessed include the number of infant infections averted, cost per infection averted, cost per disability adjusted life year (DALY) averted for infants, life years gained in HIV-infected mothers, cost per life year gained for the HIV-infected mothers and the incremental cost-effectiveness ratios for each outcome. DALYs were estimated using standard published methods [15]. We analyzed four strategies including; (1) Current practice in 2010, (2) Option A, (3) Option B, and (4) Option B+. For the current practice, we modelled the mix of interventions in Malawi including HIV testing and counselling and ARV prophylaxis for HIV-infected pregnant women at the reported coverage levels as of the end of 2010 [2].We modelled an ante-natal care (ANC) coverage of 91% according to the World Health Statistics report [7] with an HIV testing and counselling coverage of 66% in pregnant women [8]. Using data derived from a direct report from the Ministry of Health (MOH) in Malawi, of the 45% of HIV-infected pregnant women who received antiretrovirals for PMTCT in 2010, 38% received single-dose nevirapine (NVP), 25% received a dual-drug regimen containing zidovudine (AZT), 22% received triple-drug ARV prophylaxis and 15% received full ART [16]. These coverage rates were modelled as the current practice in 2010, prior to the start of the B+ programme. The options analysed and their components are shown in Table 1. In Option A, pregnant women not eligible for ART based on the disease stage were modelled to receive zidovudine from 14 weeks, a single dose of nevirapine at the onset of labour and a dual-drug regimen of zidovudine and lamivudine (AZT+3TC) for one week after delivery. In Option B, pregnant women not eligible for ART were modelled to receive triple-antiretroviral prophylaxis of tenofovir, lamivudine and efavirenz (TDF+3TC+EFV: this is the regimen adopted by Malawi) from 14 weeks until one week after all breastfeeding has stopped. In Option B+, treatment decisions are not based on CD4 count and therefore all HIV-infected pregnant women who receive HIV testing and are positive based on the prevalence rate assumptions, were modelled to initiate and continue lifelong ART. Infants receive prophylaxis with nevirapine until one week after all breastfeeding has stopped in Option A, while they receive nevirapine for six weeks after birth with current practice, Options B and B+. For all strategies, it was assumed that 42% of HIV-infected pregnant women have CD4 counts at or less than 350 cells/ µL and are eligible for ART, based on findings of a population-based study in Malawi [13]. Therefore women eligible for ART under WHO Options A and B receive ART initially in the model and women who later become eligible after delivery and breastfeeding will start to receive ART according to their disease progression and at the coverage of ART in the general population [9]. For this analysis, full ANC coverage was assumed, and all pregnant women were assumed to receive HIV testing and counselling while ARV coverage rates for prophylaxis and treatment were assumed to be 90% for the three options while the 2010 coverage levels reported by the MOH were modelled for the current practice. All the input parameters are presented in Table 2. For perinatal transmission rates, we used the recently revised mother-to-child transmission rates by the UNAIDS epidemiology reference group for use in Spectrum [17] along with published findings from the multicentre Kesho Bora study with rates of 2.7% for Option A and 1.7% for Options B and B+ for the postnatal transmission in all options [18]. Breastfeeding can contribute as much as 42% to the overall mother-to-child transmission [19]. The 2010 Demographic Health Survey for Malawi reports a mean breastfeeding duration of 23 months among all mothers [20] and study findings from Malawi report a median breastfeeding duration of 11.5 months among HIV-infected women. [21]. In this analysis, we assumed that HIV-infected mothers would breastfeed for an average of 12 months. The monthly risk of postnatal HIV transmission through breastfeeding, in the absence of any intervention was assumed to be 1.04% which is the average of the rates reported for transmission in eligible and non-eligible women by the UNAIDS epidemiology reference group [18]. Survival estimates from the model were calibrated with results from the ART-LINC, which reported data from 36,615 patients on ART from 17 cohorts in Africa, Asia and South America [22]. Transition probabilities between adjacent states for untreated women were assumed to be similar to reported findings in other populations and were estimated from the published natural history studies [23]–[28] and calculated as the reciprocals of the mean waiting times in each CD4 cell state [29]. For women receiving ART, the transition probabilities from one state to the next lower one were calculated by applying the reported relative risk of disease progression with treatment compared to no treatment of 0.27 [30]. Weighted averages from studies reporting ART survival in low-income settings were used to determine the mortality rate in each state [31]. Women receiving ART could also progress from lower to higher states based on study findings on CD4 cell recovery for people on treatment [32], but these women are assumed to remain on treatment. The model incorporates possible treatment failures, which can result from poor adherence and loss to follow up (LTFU) during treatment. For the purpose of this analysis, an adherence rate of 90% was used, as reported adherence rates in resource-limited settings are comparable to those in developed countries [33]–[34]. The cost per patient-year in each Markov state was calculated by multiplying health care utilization by the cost per person per year, based on recent cost estimates in Malawi. All costs are shown in US dollars. The cost of rapid HIV testing was $3.50 per test and all pregnant women are assumed to undergo at least one HIV test during the first antenatal visit for Options A, B and B+ while the coverage rates for ANC and HIV testing and counselling were applied for the current practice. HIV-infected pregnant women undergo CD4 cell count testing with the Current Practice, Options A and B to determine eligibility for ART at a cost of US$ 20 per test. Costs of ARVs for Options A and B included 6 months during pregnancy and 12 months during breastfeeding. The cost of drugs per woman receiving Option A for 6 months of prophylaxis is US$ 76.20, consisting of $60 for AZT and AZT+3TC, $0.20 for NVP and $16 for infant Nevirapine for 12 months of breastfeeding. The annual cost of drugs per woman receiving Option B or Option B+ is US$ 193.60 per woman. Based on the percentage distribution of regimens under the current practice as previously described, the same costs of the various regimens were applied to the current practice. Total costs of ARV prophylaxis and ART for all options are calculated for the entire period of 10 years. Other itemized costs for all the options and the current practice include early infant diagnosis testing, and cotrimoxazole prophylaxis for HIV-exposed infants. Ninety percent of all infants born to an HIV-infected mother are assumed to be tested with DNA PCR at a cost of US$ 32.50 [35]. Cotrimoxazole prophylaxis was assumed to be given to all HIV-exposed infants for a period of 12 months at a cost of US$5 per person per year to account for the time it takes to receive early-infant diagnosis (EID) results and place HIV-infected infants on treatment [36]–[37]. Costs are shown in Table 3. Cost estimates and prices were obtained directly from the Ministry of Health of Malawi, and supplemented with additional cost data from the World Health Organization Global Price Reporting Mechanism [38]. All costs are expressed in US dollars at a 2010 price base. Costs and benefits were discounted at 3% annually. The three options were compared to the current practice using incremental cost-effectiveness ratios, of US dollars per life-year gained and per disability-adjusted life-year averted. Sensitivity analysis was performed to assess the robustness of the results to changes in the assumptions made. The efficacies of ARV prophylaxis and ART on reducing peripartum and postnatal transmission rates were varied using ranges reported in the literature to take into account clinical practice situations where adherence may be lower than reported in clinical trials.
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